Zea ribosomal repeat evolution and substitution patterns

Zea and Tripsacum nuclear ribosomal internal transcribed spacer (ITS) sequences were used to evaluate patterns of concerted evolution, rates of substitutions, patterns of methylation-induced deamination, and structural constraints of the ITS. ITS pseudogenes were identified by their phylogenetic position, differences in nucleotide composition, extensive deamination at ancestral methylation sites, and substitutions resulting in low-stability secondary RNA structures. Selection was important in shaping the kinds of polymorphisms and substitutions observed in the ITS. ITS substitution rates were significantly different among the Zea taxa. Deamination of cytosines at methylation sites was a potent mutation source, but selection appeared to maintain high methylation site density throughout the ribosomal repeat except for the gene promoter. Nucleotide divergence statistics identified selectively constrained regions at the 5' ends of the ITS1 and ITS2.      

Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion

The silkmoth chorion has provided a stimulating model for the study of evolution and developmental regulation of gene families. Previous attempts at inferring relationships among chorion sequences have been based on pairwise comparisons of overall similarity, a potentially problematic approach. To remedy this, we identified the alignable regions of low sequence variability and then analyzed this restricted database by parsimony and neighbor-joining methods. At the deepest level, the chorion sequence tree is split into two branches, called "alpha" and "beta." Within each branch, early- and late-expressing genes each constitute monophyletic groups, while the situation with middle-expressing genes remains uncertain. The HcB gene family appears to be the most basal beta-branch group, but this conclusion is qualified because the effect of gene conversion on branching order is unknown. Previous studies by Eickbush and colleagues have strongly suggested that ErA, HcA, and HcB families undergo gene conversion within a gene family, whereas the ErB family does not. The occurrence of conversion correlates with a particular tree structure; namely, branch lengths are much greater at the base of the family than at higher internodes and terminal branches. These observations raise the possibility that chorion gene families are defined by gene conversion events (reticulate evolution) rather than by descent with modification (synapomorphy).      

Application of principal component analysis in clinical gait research: Identification of systematic differences between healthy and medial knee-osteoarthritic gait

For a successful completion of a movement task the motor control system has to observe a multitude of internal constraints that govern the coordination of its segments. The purpose of this study was to apply principal component (PC) analysis to detect differences in the segmental coordination between healthy subjects and patients with medial knee osteoarthritis (OA). It was hypothesized that (1) systematic differences in patterns of whole body movement would be identifiable with this method even in small sample sized groups and that (2) these differences will include compensatory movements in the OA patients in both the lower and upper body segments. Marker positions and ground reaction forces of three gait trials of 5 healthy and 5 OA participants with full body marker sets were analyzed using a principal component analysis. Group differences in the PC-scores were determined for the first 10 PC-vectors and a linear combination of those PC-vectors where differences were found defined a discriminant vector. Projecting the original trials onto this discriminant vector yielded significant group differences (t(d=8)=3.011; p=0.017) with greater upper body movement in patients with knee OA that was correlated with the medial–lateral ground reaction force. These results help to characterize the adaptation of whole-body gait patterns to knee OA in a relatively small population and may provide an improved basis for the development of interventions to modify knee load. The PC-based motion analysis offered a highly sensitive approach to identify characteristic whole body patterns of movement associated with pathological gait.     

A new parametric approach for modeling hip forces during gait

An analytical parametric model was developed to estimate the natural biological variations in muscle forces and their effect on the hip forces subject only to physiological constraints and not predefined optimization criterion. Force predictions are based on the joint kinematics and kinetics of each subject, a previously published muscle model, and physiological constraints on the muscle force distributions. The model was used to determine the hip contact forces throughout the stance phase of gait of a subject with a total hip replacement (THR). The parametrically modeled peak hip force without antagonistic muscle activity varied from 2.7 to 3.2 Body Weights (mean 2.9 Body Weights), which agreed well with published in vivo measurements from instrumented THRs in other subjects. For every 10% increase in antagonistic activity, the mean peak hip force increased by 0.2 Body Weights. The parametric model allows one to examine the effect of specific muscle weaknesses or increased antagonistic muscle activity on the hip forces. The model also provides a tool for studying the effect of gait adaptations on hip forces, as predictions are based on each individual's gait data. Differences in peak forces between subjects can then be evaluated relative to the uncertainty in not knowing the precise muscle force distributions.     

A neural network model to predict knee adduction moment during walking based on ground reaction force and anthropometric measurements

The external knee adduction moment (KAM) is a major variable for the evaluation of knee loading during walking, specifically in patients with knee osteoarthritis. However, assessment of the KAM is limited to locations where full motion laboratories are available. The purpose of this study was to develop and test a simple method to predict the KAM using only force plate and anthropometric measurements. Three groups of 28 knees (asymptomatic, mild osteoarthritis, and severe osteoarthritis) were studied. Walking trials were collected at different speeds using a motion capture system and a force plate. The reference KAM was calculated by inverse dynamics. For the prediction, inter-subject artificial neural networks were designed using 11 inputs coming from the ground reaction force and the mechanical axis alignment. The predicted KAM curves were similar to the reference curves with median mean absolute deviation (MAD) of 0.36%BW*Ht and median correlation coefficient of 0.966 over 756 individual trials. When comparing mean group curves, the median MAD was 0.09%BW*Ht and the median correlation coefficient 0.998. The peak values and the angular impulses extracted from the predicted and reference curves were significantly correlated, and the same significant differences were obtained among the three groups when the predicted or when the reference curves were used for 95% of the comparisons. In conclusion, this study demonstrated that a simple method using a generic artificial neural network can predict the KAM curve during walking with a high level of significance and provides a practical option for a broader evaluation of the KAM.     

Direct comparison of measured and calculated total knee replacement force envelopes during walking in the presence of normal and abnormal gait patterns

Knee joint forces measured from instrumented implants provide important information for testing the validity of computational models that predict knee joint forces. The purpose of this study was to validate a parametric numerical model for predicting knee joint contact forces against measurements from four subjects with instrumented TKRs during the stance phase of gait. Model sensitivity to abnormal gait patterns was also investigated. The results demonstrated good agreement for three subjects with relatively normal gait patterns, where the difference between the mean measured and calculated forces ranged from 0.05 to 0.45 body weights, and the envelopes of measured and calculated forces (from three walking trials) overlapped. The fourth subject, who had a "quadriceps avoidance" external moment pattern, initially had little overlap between the measured and calculated force envelopes. When additional constraints were added, tailored to the subject's gait pattern, the model predictions improved to complete force envelope overlap. Coefficient of multiple determination analysis indicated that the shape of the measured and calculated force waveforms were similar for all subjects (adjusted coefficient of multiple correlation values between 0.88 and 0.92). The parametric model was accurate in predicting both the magnitude and waveform of the contact force, and the accuracy of model predictions was affected by deviations from normal gait patterns. Equally important, the envelope of forces generated by the range of solutions substantially overlapped with the corresponding measured envelope from multiple gait trials for a given subject, suggesting that the variable strategic processes of in vivo force generation are covered by the solution range of this parametric model.     

A variable-stiffness shoe lowers the knee adduction moment in subjects with symptoms of medial compartment knee osteoarthritis

The purpose of this study was to evaluate the effectiveness of variable-stiffness shoes in lowering the peak external knee adduction moment during walking in subjects with symptomatic medial compartment knee osteoarthritis. The influence on other lower extremity joints was also investigated. The following hypotheses were tested: (1) variable-stiffness shoes will lower the knee adduction moment in the symptomatic knee compared to control shoes; (2) reductions in knee adduction moment will be greater at faster speeds; (3) subjects with higher initial knee adduction moments in control shoes will have greater reductions in knee adduction moment with the intervention shoes; and (4) variable-stiffness shoes will cause secondary changes in the hip and ankle frontal plane moments. Seventy-nine individuals were tested at self-selected slow, normal, and fast speeds with a constant-stiffness control shoe and a variable-stiffness intervention shoe. Peak moments for each condition were assessed using a motion capture system and force plate. The intervention shoes reduced the peak knee adduction moment compared to control at all walking speeds, and reductions increased with increasing walking speed. The magnitude of the knee adduction moment prior to intervention explained only 11.9% of the variance in the absolute change in maximum knee adduction moment. Secondary changes in frontal plane moments showed primarily reductions in other lower extremity joints. This study showed that the variable-stiffness shoe reduced the knee adduction moment in subjects with medial compartment knee osteoarthritis without the discomfort of a fixed wedge or overloading other joints, and thus can potentially slow the progression of knee osteoarthritis.     

Implications of increased medio-lateral trunk sway for ambulatory mechanics

The purposes of this study was to test a mechanism to reduce the knee adduction moment by testing the hypothesis that increased medio-lateral trunk sway can reduce the knee adduction moment during ambulation in healthy subjects, and to examine the possibility that increasing medio-lateral trunk sway can produce similar potentially adverse secondary gait changes previously associated with reduced knee adduction moments in patients with knee osteoarthritis. Nineteen healthy adults performed walking trials with normal and increased medio-lateral trunk sway at a self-selected normal walking speed. Standard gait analysis was used to calculate three-dimensional lower extremity joint kinematics and kinetics. Knee and hip adduction moments were lower (-65.0% and -57.1%, respectively) for the increased medio-lateral trunk sway trials than for the normal trunk sway trials. Knee flexion angle at heel-strike was 3 degrees higher for the increased than for the normal trunk sway trials. Knee and hip abduction moments were higher for the increased medio-lateral trunk sway trials, and none of the other variables differed between the two conditions. Walking with increased medio-lateral trunk sway substantially reduces the knee adduction moment during walking in healthy subjects without some of the adverse secondary effects such as increased axial loading rates at the major joints of the lower extremity. This result supports the potential of using gait retraining for walking with increased medio-lateral trunk sway as treatment for patients with degenerative joint disease such as medial compartment knee osteoarthritis.